Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
BMC Complement Med Ther. 2023 Apr 24;23(1):130. doi: 10.1186/s12906-023-03944-7.
With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide.
Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes.
With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking.
The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.
随着发病率的快速上升，甲状腺乳头状癌（PTC）是最常见的头颈部癌症。小白菊内酯是一种从中药中分离出来的物质，它可以抑制多种癌细胞，包括 PTC 细胞。本研究旨在探讨小白菊内酯处理 PTC 细胞后的脂质谱和脂质变化。
采用 UHPLC/Q-TOF-MS 平台对小白菊内酯处理的 PTC 细胞进行全面的脂质组学分析，探讨改变的脂质谱和特定的改变脂质种类。进行网络药理学和分子对接，以显示小白菊内酯、改变的脂质种类和潜在靶基因之间的关联。
该研究具有较高的稳定性和重现性，共鉴定出 34 种脂质类别和 1736 种脂质种类。脂质类别分析表明，小白菊内酯处理的 PTC 细胞中含有更高水平的脂肪酸（FA）、胆固醇酯（ChE）、简单神经酰胺 G3（CerG3）和溶血磷脂酰甘油（LPG），而神经酰胺 Zyme（ZyE）和单半乳糖二酰基甘油（MGDG）水平较低，但与对照组相比无显著差异。小白菊内酯处理的 PTC 细胞中，几种特定的脂质种类发生了显著变化，包括磷脂酰胆碱（PC）（12:0e/16:0）、PC（18:0/20:4）、CerG3（d18:1/24:1）、溶血磷脂酰乙醇胺（LPE）（18:0）、磷脂酰肌醇（PI）（19:0/20:4）、溶血磷脂酰胆碱（LPC）（28:0）、胆固醇酯（ChE）（22:6）的增加，以及磷脂酰乙醇胺（PE）（16:1/17:0）、PC（34:1）和 PC（16:0p/18:0）的减少。通过网络药理学和脂质组学相结合，发现了四个关键靶点（PLA2G4A、LCAT、LRAT 和 PLA2G2A）。其中，分子对接证实 PLA2G2A 和 PLA2G4A 能够与小白菊内酯结合。
观察到小白菊内酯处理的 PTC 细胞中改变的脂质谱和几种明显改变的脂质种类。这些改变的脂质种类，如 PC（34:1）和 PC（16:0p/18:0），可能参与了小白菊内酯的抗肿瘤机制。PLA2G2A 和 PLA2G4A 可能在小白菊内酯处理 PTC 细胞时发挥关键作用。
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